- Main
An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike
- Schoof, Michael;
- Faust, Bryan;
- Saunders, Reuben A;
- Sangwan, Smriti;
- Rezelj, Veronica;
- Hoppe, Nick;
- Boone, Morgane;
- Billesbølle, Christian B;
- Puchades, Cristina;
- Azumaya, Caleigh M;
- Kratochvil, Huong T;
- Zimanyi, Marcell;
- Deshpande, Ishan;
- Liang, Jiahao;
- Dickinson, Sasha;
- Nguyen, Henry C;
- Chio, Cynthia M;
- Merz, Gregory E;
- Thompson, Michael C;
- Diwanji, Devan;
- Schaefer, Kaitlin;
- Anand, Aditya A;
- Dobzinski, Niv;
- Zha, Beth Shoshana;
- Simoneau, Camille R;
- Leon, Kristoffer;
- White, Kris M;
- Chio, Un Seng;
- Gupta, Meghna;
- Jin, Mingliang;
- Li, Fei;
- Liu, Yanxin;
- Zhang, Kaihua;
- Bulkley, David;
- Sun, Ming;
- Smith, Amber M;
- Rizo, Alexandrea N;
- Moss, Frank;
- Brilot, Axel F;
- Pourmal, Sergei;
- Trenker, Raphael;
- Pospiech, Thomas;
- Gupta, Sayan;
- Barsi-Rhyne, Benjamin;
- Belyy, Vladislav;
- Barile-Hill, Andrew W;
- Nock, Silke;
- Liu, Yuwei;
- Krogan, Nevan J;
- Ralston, Corie Y;
- Swaney, Danielle L;
- García-Sastre, Adolfo;
- Ott, Melanie;
- Vignuzzi, Marco;
- Walter, Peter;
- Manglik, Aashish;
- Azumaya, Caleigh M;
- Puchades, Cristina;
- Sun, Ming;
- Braxton, Julian R;
- Brilot, Axel F;
- Gupta, Meghna;
- Li, Fei;
- Lopez, Kyle E;
- Melo, Arthur;
- Merz, Gregory E;
- Moss, Frank;
- Paulino, Joana;
- Pospiech, Thomas H;
- Pourmal, Sergei;
- Rizo, Alexandrea N;
- Smith, Amber M;
- Thomas, Paul V;
- Wang, Feng;
- Yu, Zanlin;
- Dickinson, Miles Sasha;
- Nguyen, Henry C;
- Asarnow, Daniel;
- Campbell, Melody G;
- Chio, Cynthia M;
- Chio, Un Seng;
- Diwanji, Devan;
- Faust, Bryan;
- Gupta, Meghna;
- Hoppe, Nick;
- Jin, Mingliang;
- Li, Junrui;
- Liu, Yanxin;
- Merz, Gregory E;
- Sangwan, Smriti;
- Tsui, Tsz Kin Martin;
- Trenker, Raphael;
- Trinidad, Donovan;
- Tse, Eric;
- Zhang, Kaihua;
- Zhou, Fengbo;
- Herrera, Nadia;
- Kratochvil, Huong T;
- Schulze-Gahmen, Ursula;
- Thompson, Michael C;
- Young, Iris D;
- Biel, Justin;
- Deshpande, Ishan;
- Liu, Xi;
- Billesbølle, Christian Bache;
- Nowotny, Carlos;
- Smith, Amber M;
- Zhao, Jianhua;
- Bowen, Alisa;
- Hoppe, Nick;
- Li, Yen-Li;
- Nguyen, Phuong;
- Safari, Mali;
- Schaefer, Kaitlin;
- Whitis, Natalie;
- Moritz, Michelle;
- Owens, Tristan W;
- Diallo, Amy;
- Kim, Kate;
- Peters, Jessica K;
- Titus, Erron W;
- Chen, Jenny;
- Doan, Loan;
- Flores, Sebastian;
- Lam, Victor L;
- Li, Yang;
- Lo, Megan;
- Thwin, Aye C;
- Wankowicz, Stephanie;
- Zhang, Yang;
- Bulkley, David;
- Joves, Arceli;
- Joves, Almarie;
- McKay, Liam;
- Tabios, Mariano;
- Rosenberg, Oren S;
- Verba, Kliment A;
- Agard, David A;
- Cheng, Yifan;
- Fraser, James S;
- Frost, Adam;
- Jura, Natalia;
- Kortemme, Tanja;
- Krogan, Nevan J;
- Manglik, Aashish;
- Southworth, Daniel R;
- Stroud, Robert M
- et al.
Published Web Location
https://doi.org/10.1126/science.abe3255Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enters host cells via an interaction between its Spike protein and the host cell receptor angiotensin-converting enzyme 2 (ACE2). By screening a yeast surface-displayed library of synthetic nanobody sequences, we developed nanobodies that disrupt the interaction between Spike and ACE2. Cryo-electron microscopy (cryo-EM) revealed that one nanobody, Nb6, binds Spike in a fully inactive conformation with its receptor binding domains locked into their inaccessible down state, incapable of binding ACE2. Affinity maturation and structure-guided design of multivalency yielded a trivalent nanobody, mNb6-tri, with femtomolar affinity for Spike and picomolar neutralization of SARS-CoV-2 infection. mNb6-tri retains function after aerosolization, lyophilization, and heat treatment, which enables aerosol-mediated delivery of this potent neutralizer directly to the airway epithelia.
Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.
Main Content
Enter the password to open this PDF file:
-
-
-
-
-
-
-
-
-
-
-
-
-
-